Enzyme sequestration by the substrate: An analysis in the deterministic and stochastic domains

PLoS Computational Biology
Andreas Petrides, Glenn Vinnicombe

Abstract

This paper is concerned with the potential multistability of protein concentrations in the cell. That is, situations where one, or a family of, proteins may sit at one of two or more different steady state concentrations in otherwise identical cells, and in spite of them being in the same environment. For models of multisite protein phosphorylation for example, in the presence of excess substrate, it has been shown that the achievable number of stable steady states can increase linearly with the number of phosphosites available. In this paper, we analyse the consequences of adding enzyme docking to these and similar models, with the resultant sequestration of phosphatase and kinase by the fully unphosphorylated and by the fully phosphorylated substrates respectively. In the large molecule numbers limit, where deterministic analysis is applicable, we prove that there are always values for these rates of sequestration which, when exceeded, limit the extent of multistability. For the models considered here, these numbers are much smaller than the affinity of the enzymes to the substrate when it is in a modifiable state. As substrate enzyme-sequestration is increased, we further prove that the number of steady states will inevitabl...Continue Reading

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